Modeling the Breakage-Fusion-Bridge Mechanism: Combinatorics and Cancer Genomics
The breakage-fusion-bridge (BFB) mechanism was proposed over seven decades ago and is a source of genomic variability and gene amplification in cancer. Here we formally model and analyze the BFB mechanism, to our knowledge this first time this has been undertaken. We show that BFB can be modeled as successive inverted prefix duplications of a string. Using this model, we show that BFB can achieve a surprisingly broad range of amplification patterns. We find that a sequence of BFB operations can be found that nearly fits most patterns of copy number increases along a chromosome. We conclude that this limits the usefulness of methods like array CGH for detecting BFB and discuss other implications for understanding mechanisms of genomic instability.
Keywordscancer genomics algorithms combinatorial pattern matching gene amplification
Unable to display preview. Download preview PDF.
- 2.Bignell, G.R., Santarius, T., Pole, J.C., Butler, A.P., Perry, J., Pleasance, E., Greenman, C., Menzies, A., Taylor, S., Edkins, S., Campbell, P., Quail, M., Plumb, B., Matthews, L., McLay, K., Edwards, P.A., Rogers, J., Wooster, R., Futreal, P.A., Stratton, M.R.: Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution. Genome Res. 17, 1296–1303 (2007)CrossRefGoogle Scholar
- 3.Deza, M.M., Deza, E.: Encyclopedia of Distances. Springer (2009)Google Scholar
- 5.McClintock, B.: The Production of Homozygous Deficient Tissues with Mutant Characteristics by Means of the Aberrant Mitotic Behavior of Ring-Shaped Chromosomes. Genetics 23, 315–376 (1938)Google Scholar
- 6.McClintock, B.: The Stability of Broken Ends of Chromosomes in Zea Mays. Genetics 26, 234–282 (1941)Google Scholar
- 9.Zhao, X., Li, C., Paez, J.G., Chin, K., Janne, P.A., Chen, T.H., Girard, L., Minna, J., Christiani, D., Leo, C., Gray, J.W., Sellers, W.R., Meyerson, M.: An integrated view of copy number and allelic alterations in the cancer genome using single nucleotide polymorphism arrays. Cancer Res. 64, 3060–3071 (2004)CrossRefGoogle Scholar